Despite the widespread use of narcotics for centuries, a firm understanding of the circulatory effects of these agents has yet to be achieved. Part of the problem stems from the marked variability of reactions to these agents by different species. In human subjects, morphine appears to dilate limb resistance vessels through an indirect mechanism via a central nervous system reduction in alpha-adrenergic tone. The first objective of the proposed research is to determine whether or not morphine and related narcotics (meperidine or fentanyl) alter the peripheral arteriolar constrictor responses to hypercapnia. Forearm blood flow will be measured plethysmo-graphically and forearm vascular resistance calculated before and during carbon dioxide inhalation utilizing a rebreathing or steady state technique. Epinephrine iontophoresis will be utilized to differentiate the effects of narcotics and hypercapnia on skin and muscle resistance vessels; phentolamine and propranolol regional limb blockade will be utilized to differentiate direct from neurohumoral effects of hypercapnia. The second major objective will be to determine the effects of narcotics on the splanchnic resistance vessels using the indocyanine green constant infusion method to estimate splanchnic blood flow in normal subjects and patients with left and right heart failure. Lastly, a technique to evaluate splanchnic blood volume will be investigated in a canine model with the hope that this can be applied to human subjects. Thus, it is hoped to define more precisely the mechanism of the arteriolar dilation produced by narcotics, to see whether this effect predominates in the splanchnic circulation where significant pooling of blood may occur. The more precise definition of the pharmacologic action of these commonly used therapeutic agents has considerable clinical relevance.